Alisa N. Femia

Cutaneous Dermatomyositis: An Updated Review of Treatment Options and Internal Associations

Dermatomyositis is a specific type of inflammatory myopathy with characteristic cutaneous findings. Patients may have skin disease without clinically apparent muscle disease, but this disorder is best thought of as a systemic process. Therefore, all patients with dermatomyositis skin lesions need appropriate evaluation for muscle disease, esophageal dysfunction, cardiopulmonary disease, and potential internal malignancy. There are many therapies that have been used for patients with dermatomyositis, but most are based upon case series or expert opinion rather than meta-analyses or randomized, placebo-controlled trials. Even those therapies that have been subjected to randomized, blinded, placebo-controlled trials include a mixture of patients with idiopathic inflammatory myopathy and do not utilize a validated assessment tool for measuring cutaneous disease responses. In this review, we discuss the therapies available as well as the internal associations with dermatomyositis.

Dermatomyositis Induced by Anti–Tumor Necrosis Factor in a Patient With Juvenile Idiopathic Arthritis

IMPORTANCE Biologic therapies, including anti-tumor necrosis factor (TNF) agents, are increasingly used to treat a variety of autoimmune diseases. Paradoxically, these agents have been reported to induce some of the very diseases they were designed to treat, including dermatomyositis (DM). We describe the first case of anti-TNF-associated DM without muscle involvement presenting in an adult patient with a history of arthritis since childhood. This cutaneous eruption recurred after rechallenge with an alternate anti-TNF agent. OBSERVATIONS A 46-year-old man with juvenile idiopathic arthritis developed a pruritic cutaneous eruption while receiving etanercept. Given concern about a drug-induced eruption, etanercept therapy was discontinued and the cutaneous findings improved. However, after rechallenge with adalimumab, he developed similar findings consistent with the skin manifestations of DM. After discontinuation of all anti-TNF drug therapy and the addition of methotrexate sodium, his eruption improved. CONCLUSIONS AND RELEVANCE Because the use of these agents is increasing, practitioners should be aware of the possibility of anti-TNF-induced autoimmune disorders, including DM. The case described herein is unique in that anti-TNF-induced autoimmune disease occurred in a patient with existing arthritis since childhood and recurred with rechallenge, adding further evidence to support the existence of anti-TNF-induced DM.

Treatment Options for Pityriasis Rubra Pilaris Including Biologic Agents: A Retrospective Analysis From an Academic Medical Center

Treatment Options for Pityriasis Rubra Pilaris Including Biologic Agents: A Retrospective Analysis From an Academic Medical Center Pityriasis rubra pilaris (PRP) is characterized by hyperkeratotic papules, palmoplantar keratoderma, and widespread erythema with islands of sparing. Treatment is challenging, and a standard therapeutic protocol does not exist. Given the paucity of available therapeutic data, we assessed the clinical presentation of PRP and clinical response (CR) to therapy at 2 teaching hospitals in Boston, Massachusetts. In addition, we aimed to determine the role of systemic and biologic agents.

Epidemiology and Treatment of Eosinophilic Fasciitis: An Analysis of 63 Patients From 3 Tertiary Care Centers

Author Contributions: Drs Hubiche and Valério had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hubiche, Valério, del Giudice. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Hubiche, Valério, del Giudice. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Hubiche, Valério. Administrative, technical, or material support: Hubiche, Mahe, Phan. Study supervision: Hubiche, Boralevi, Bodemer Skandalis, del Giudice.

Paraproteinemia-Associated Scleredema Treated Successfully With Intravenous Immunoglobulin

Discussion | There have been a variety of treatment techniques used for CRDD, including cryotherapy, surgical excision, irradiation, oral corticosteroids, dapsone, thalidomide, and isotretinoin. To our knowledge, the use of methotrexate alone or in combination with other agents has been reported in 9 cases of systemic Rosai-Dorfman, and a complete to partial response was reported in most cases.4 By contrast, methotrexate therapy has been reported in only 3 cases of CRDD, and partial or no improvement was reported.3,5,6 However, in all of these cases, the eruption had already been present for well over a year. In our patient, a lack of response to prednisone, preexisting diabetes, and significant disease burden prompted the choice of low-dose methotrexate, to which a complete clinical response was seen over 11 months. Though the exact cause of CRDD remains unknown, the presence of Epstein-Barr virus, human herpesvirus 6 by polymerase chain reaction, and reported eruption after vaccination7 with spontaneous remission over months to years suggests that CRDD is a benign reactive process involving a particular pattern of immune dysregulation. Early diagnosis remains a challenge in CRDD owing to its nonspecific clinical manifestations, including variable numbers of papules, nodules, plaques, or tumors. Timely diagnosis and initiation of methotrexate therapy may be key to effecting a rapid clinical remission while this disease remains in its active phase.

Toward Improved Understanding of a Potential Association between Isotretinoin and Inflammatory Bowel Disease

Isotretinoin is a widely prescribed medication for nodulocystic acne. Existing literature is conflicting regarding an association between isotretinoin and inflammatory bowel disease. In this issue, Alhusayen et al. report findings from a 12-year observational study exploring a possible association, and they conclude that acne itself may be responsible for an apparent correlation.

Development and Pilot Testing of the Cutaneous Lupus Screening Tool

IMPORTANCE Patients with cutaneous lupus erythematosus (CLE) experience significant morbidity and poor quality of life. In the absence of a dermatologists examination, no reliable tool exists to confirm whether a patient has CLE for use in epidemiologic studies. OBJECTIVE To determine whether the Cutaneous Lupus Screening (CLUSE) tool can detect cases of CLE by measuring its performance in individuals with dermatologist-diagnosed CLE compared with individuals without CLE. DESIGN, SETTING, AND PARTICIPANTS The CLUSE tool is a novel, self-administered questionnaire with 15 closed-ended questions derived from the Delphi method. It includes features of disease validation for CLE as well as its most common phenotypes. This pilot study was administered during a 1-year period (July 1, 2011, to June 30, 2012) in outpatient dermatology clinics at an academic medical center. Data analysis was performed July 1, 2012, to November 30, 2013. Participants were individuals 18 years or older who had a definitive diagnosis of CLE or any other non-CLE dermatologic condition as established by a board-certified dermatologist. Eligible patients were recruited consecutively, and no individual approached declined to participate. MAIN OUTCOMES AND MEASURES Sensitivity and specificity of the individual questions from the CLUSE tool in predicting CLE, comparisons between summary scores for the dichotomous questions between the CLE cases and non-CLE controls, and 9 scoring algorithms that assign a diagnosis of CLE and its subtypes depending on an individuals response to each question. RESULTS A total of 133 patients were given the CLUSE tool; 16 participants were excluded. Responses from 117 individuals were collected for analysis and included 24 CLE cases and 93 non-CLE cases. In the 117 questionnaires analyzed, mean (SD) and median (interquartile range) CLUSE scores differed in the CLE (5.6 [2.1] and 5.5 [3-10], respectively) vs non-CLE (0.96 [1.6] and 0 [0-7], respectively) groups (all P < .001). Of the 9 algorithms, algorithm 9, used for diagnosing CLE regardless of subtype, demonstrated the highest sensitivity (87.5%) and high specificity (96.8%). CONCLUSIONS AND RELEVANCE A combination of questions and representative photographs can ascertain cases of CLE with high sensitivity and specificity. The CLUSE tool is a brief, self-administered questionnaire with low respondent burden used for the identification of CLE. In the future, this questionnaire will be administered to large, established patient databases to gather epidemiologic data on this disease.

Raynaud’s phenomenon: Current concepts

Raynauds phenomenon (RP) is a transient, acral, vasospastic phenomenon that manifests with characteristic color changes. This vasospasm, classically triggered by cold temperatures, may also be driven by shifts in temperature, climate, or emotional state. Primary RP (PRP) is a common condition without severe sequelae. Secondary RP (SRP), which may be driven by vascular, autoimmune, hematologic, or endocrine etiologies, can result in digital ulceration, irreversible ischemia and necrosis, and secondary infection. This review delineates the clinical manifestations of both primary and secondary RP, as well as the current understanding of RP epidemiology and pathogenesis. Proper examination, including nailfold capillary microscopy, and laboratory workup for secondary causes of RP are also discussed. The traditional armamentarium of therapies used for RP, as well as newer medical and surgical options, is also summarized with particular regard to the clinical evidence for their efficacy.

Erythema nodosum in association with idiopathic granulomatous mastitis: a case series and review of the literature

metastases (Fig. 1). Disease stabilized for about 1 year until progression of cervical metastases occurred and radiotherapy was performed. Because of a new paraaortal lesion, treatment with nivolumab was initiated. Histological assessment of tissue from a cervical lymph node metastasis resected before therapy with ipilimumab revealed a dense infiltration of CD4(+) and CD8(+) T cells as a potential marker for treatment response. The third patient received therapy with ipilimumab after surgical resection of inguinal and iliac lymph node metastases. Because of elevated serum pancreatic enzymes (grade 4), therapy was stopped after three cycles. When disease progression occurred a few months later, radiation to the retroperitoneal and pelvic lymph nodes was conducted. Further on, rapid disease progression occurred. The fourth patient underwent radiotherapy of a growing paraaortal lymph node before adjuvant therapy with ipilimumab was initiated. Imaging was without any suspicious findings for more than 1 year when retrocrural F-FDG enrichment was found. Another radiation therapy was performed, and four more cycles of ipilimumab administered. Thereafter, PET/CT scans were without any evidence of vital tumour tissue. Due to disease recurrence, the fifth patient received radiation to right iliac lymph node metastases. Thereafter, PET/CT scans revealed persistent F-FDG uptake, and ipilimumab was administered. Since then follow-up imaging was without any evidence of tumour recurrence. Altogether, our case series emphasizes a potential role of ipilimumab within a multimodal therapeutic approach. Estimated median progression-free survival by Kaplan–Meier was 12.0 months [0.0; 27.3]. Median overall survival has not yet been reached. Taking into account that all patients experienced disease recurrence repeatedly and had advanced disease, our cases indicate activity of ipilimumab in MCC. To date, there is only one report on a patient who achieved a reduction in cutaneous MCC lesions during therapy with ipilimumab and chemotherapy. Predisposing factors for immunotherapy in MCC need to be further defined. Immune infiltration may be a positive predictor for outcome. Taking into account improved efficacy of ipilimumab at limited tumour burden, it seems worthwhile to monitor LDH values during therapy. We found favourable treatment response in patients who received ipilimumab after radiotherapy. Synergism of immunotherapy and radiotherapy is a known phenomenon. Adjuvant ipilimumab in completely resected MCC is currently studied in a clinical trial in Europe (ADMEC, NCT02196961). Compared to antiPD-1 antibodies, ipilimumab might have the advantage of a short treatment period in usually elderly patients. Additionally, it seems worthwhile to evaluate combined therapy of ipilimumab and an anti-PD-1 antibody in metastatic MCC. J.K. Winkler,* A. Dimitrakopoulou-Strauss, C. Sachpekidis, A. Enk, J.C. Hassel Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany *Correspondence: J.K. Winkler. E-mail: julia.winkler@med.uniheidelberg.de

Characteristics and Alternative Treatment Outcomes of Antimalarial-Refractory Cutaneous Lupus Erythematosus

Centre for Cardiovascular Research (DZHK), partner site Greifswald, Germany (Gross, Völzke, Nauck); Department of Cardiology, University Medicine Greifswald, Germany (Gross); Institute for Community Medicine, University Medicine Greifswald, Germany (Völzke); German Centre for Diabetes Research (DZD), partner site Greifswald, Germany (Völzke); European University of Applied Sciences, Faculty of Applied Public Health, Rostock, Germany (Haring); School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia (Haring). Corresponding Author: Hanna Kische, Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch Str D-17475 Greifswald (kischeh@uni-greifswald.de). Accepted for Publication: January 25, 2017. Published Online: April 12, 2017. doi:10.1001/jamadermatol.2017.0297 Author Contributions: Drs Kische and Haring, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Wallaschofski, Nauck, Haring. Acquisition, analysis, or interpretation of data: Kische, Arnold, Gross, Wallaschofski, Völzke, Haring. Drafting of the manuscript: Kische, Nauck, Haring. Critical revision of the manuscript for important intellectual content: Arnold, Gross, Wallaschofski, Völzke, Haring. Statistical analysis: Kische, Gross. Obtained funding: Völzke. Administrative, technical, or material support: Arnold, Völzke, Haring. Supervision: Wallaschofski, Nauck, Haring. Conflict Interest Disclosures: None reported. Funding/Support: This study was supported in part by the Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. This work is also part of the research project Greifswald Approach to Individualized Medicine. Role of the Funder/Sponsor: The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Sinclair R, Torkamani N, Jones L. Androgenetic alopecia: new insights into the pathogenesis and mechanism of hair loss. F1000Res. 2015;4(F1000 Faculty Rev):585. doi:10.12688/f1000research.6401.1 2. Kondo S, Hozumi Y, Aso K. Organ culture of human scalp hair follicles: effect of testosterone and oestrogen on hair growth. Arch Dermatol Res. 1990;282(7): 442-445. 3. Völzke H, Alte D, Schmidt CO, et al. Cohort profile: the study of health in Pomerania. Int J Epidemiol. 2011;40(2):294-307. 4. Haring R, Hannemann A, John U, et al. Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab. 2012;97(2):408-415. 5. Sanke S, Chander R, Jain A, Garg T, Yadav P. A comparison of the hormonal profile of early androgenetic alopecia in men with the phenotypic equivalent of polycystic ovarian syndrome in women. JAMA Dermatol. 2016;152(9):986-991. 6. Narad S, Pande S, Gupta M, Chari S. Hormonal profile in Indian men with premature androgenetic alopecia. Int J Trichology. 2013;5(2):69-72.